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Irreversible brain damage or death occurs when the brain is not getting enough oxygen.

If the brain continues its metabolism without oxygen it induces neuronal cell death.

The mechanism is called anoxic depolarization. Sodium–potassium pumps in the cell walls need to work to maintain K+ and Na+ ion gradient. When the pump runs out of energy it causes glutamate and aspartate concentrations inside the cell grow. When they grow past some critical threshold, it starts programmed cell death.

Cooling he body and brain can prevent this when the brain metabolism slows down to match the lower oxygen levels.